Expression of fatty acid synthase genes and their role in development and arboviral infection of Aedes aegypti.

BACKGROUND: Fatty acids are the building blocks of complex lipids essential for living organisms. In mosquitoes, fatty acids are involved in cell membrane production, energy conservation and expenditure, innate immunity, development and reproduction. Fatty acids are synthesized by a multifunctional enzyme complex called fatty acid synthase (FAS). Several paralogues of FAS were found in the Aedes aegypti mosquito. However, the molecular characteristics and expression of some of these paralogues have not been investigated. METHODS: Genome assemblies of Ae. aegypti were analyzed, and orthologues of human FAS was identified. Phylogenetic analysis and in silico molecular characterization were performed to identify the functional domains of the Ae. aegypti FAS (AaFAS). Quantitative analysis and loss-of-function experiments were performed to determine the significance of different AaFAS transcripts in various stages of development, expression following different diets and the impact of AaFAS on dengue virus, serotype 2 (DENV2) infection and transmission. RESULTS: We identified seven putative FAS genes in the Ae. aegypti genome assembly, based on nucleotide similarity to the FAS proteins (tBLASTn) of humans, other mosquitoes and invertebrates. Bioinformatics and molecular analyses suggested that only five of the AaFAS genes produce mRNA and therefore represent complete gene models. Expression levels of AaFAS varied among developmental stages and between male and female Ae. aegypti. Quantitative analyses revealed that expression of AaFAS1, the putative orthologue of the human FAS, was highest in adult females. Transient knockdown (KD) of AaFAS1 did not induce a complete compensation by other AaFAS genes but limited DENV2 infection of Aag2 cells in culture and the midgut of the mosquito. CONCLUSION: AaFAS1 is the predominant AaFAS in adult mosquitoes. It has the highest amino acid similarity to human FAS and contains all enzymatic domains typical of human FAS. AaFAS1 also facilitated DENV2 replication in both cell culture and in mosquito midguts. Our data suggest that AaFAS1 may play a role in transmission of dengue viruses and could represent a target for intervention strategies.

Arteriovenous Fistula Versus Graft Access Strategy in Older Adults Receiving Hemodialysis: A Pilot Randomized Trial.

BACKGROUND: It is unclear whether surgical placement of an arteriovenous (AV) fistula (AVF) confers substantial clinical benefits over an AV graft (AVG) in older adults with end-stage kidney disease (ESKD). We report vascular access outcomes of a pilot clinical trial. STUDY DESIGN: Pilot randomized parallel-group open-label trial. SETTING & PARTICIPANTS: Patients 65 years and older with ESKD and no prior AV access receiving maintenance hemodialysis through a tunneled central venous catheter referred for AV access placement by their treating nephrologist. INTERVENTION: Participants were randomly assigned in a 1:1 ratio to surgical placement of an AVG or AVF. OUTCOMES: Index AV access primary failure, successful cannulation, adjuvant interventions and infections. RESULTS: Of 122 older adults receiving hemodialysis and no prior AV access surgery, 24% died before (n = 18) or were too sick for (n = 11) referral for a permanent AV access. Of 46 eligible patients, 36 (78%) consented and were randomly assigned to AVG (n = 18) and AVF (n = 18) placement, of whom 13 (72%) and 16 (89%) underwent index AV access surgical placement, respectively. At a median follow-up of 321.0 days, primary AV access failure was noted in 31% in each group. The proportion of patients with successful cannulation was 62% (8 of 13) in the AVG and 50% (8 of 16) in the AVF group; median times to successful cannulation were 75.0 and 113.5 days, respectively. Endovascular procedures were recorded in 38% and 44%, and surgical reinterventions, in 23% and 25%, respectively. AV access infection was seen in 3 (23%) and 2 (13%) patients, respectively. LIMITATIONS: Small sample size precludes statistical inference. CONCLUSIONS: Almost one-quarter of older adults with incident ESKD and a central venous catheter as primary access were not referred for AV access placement due to medical reasons. Based on these limited results, there is little reason to favor either an AVF or AVG in this population until results from a larger randomized clinical trial become available. FUNDING: Government funding to an author (Dr Murea is supported by National Institutes of Health∖National Institute on Aging grant 1R03 AG060178-01). TRIAL REGISTRATION: NCT03545113.

Tratamientos prostodónticos en adultos mayores realizados en un centro dental especializado entre los años 2016 y 2018 / Prosthodontic treatments in older adults performed in a specialized dental center between 2016 and 2018

RESUMEN Los Adultos Mayores (AM) son más propensos a sufrir enfermedades y comorbilidades que afectan su estado bucal, por lo que necesitan de tratamientos prostodónticos acondicionados a su estado sistémico para devolverles la función masticatoria, estética y armonía oral. No obstante, la pobre cultura de prevención y la falta de profesionales especializados en su atención dificulta en gran medida esta labor. Objetivo: Determinar los tratamientos prostodónticos en pacientes adultos mayores realizados en el Servicio de Estomatología en Pacientes Especiales del Centro Dental Docente Cayetano Heredia desde abril de 2016 hasta diciembre de 2018. Material y métodos: Se realizó un estudio observacional, descriptivo, transversal y retrospectivo en una muestra de 144 AM con 200 tratamientos realizados. Se consideraron variables demográficas como sexo, grupo etario y procedencia. Se elaboró una base de datos, y posteriormente tablas de contenido para el análisis de sus resultados. Resultados: La PPR fue el tratamiento más realizado para ambos sexos, 39,8% (n=57) para el sexo femenino y 38,6% (n=22) para el sexo masculino. De acuerdo al grupo etario, los viejos-viejos fueron los pacientes que más PPR se realizaron con 40,19% (n=43). La mayoría de los pacientes provenientes de Lima Norte se realizaron el tratamiento de PPR con 41.96% (n=47). Conclusiones: Las prótesis removibles predominaron más que las fijas, siendo la PPR la que más se realizó. También se evidencio que el sexo femenino recibió más tratamientos prostodónticos y que el lugar de procedencia que más se registro fue el de Lima Norte, posiblemente por la cercanía al centro dental.

SUMMARY Older adults are more prone to suffer diseases and comorbidities that affect their oral condition, so they need prosthodontic treatments conditioned to their systemic state to restore their masticatory, aesthetic and oral harmony function. However, the poor culture of prevention and the lack of specialized professionals in their care greatly hinders this work. Objective: To determine the prosthodontic treatments in older adults performed in the Service of Estomatología in Pacientes Especiales of the Centro Dental Docente Cayetano Heredia from april 2016 to december 2018. Material and methods: An observational, descriptive, cross-sectional, and retrospective study was carried out in a sample of 144 older adults with 200 treatments performed. Demographic variables such as sex, age group and origin wereconsidered. A database was developed, and later tables of contents for the analysis of its results. Results: PPR was the most performed treatment for both sexes, 39.8% (n = 57) for the female sex and 38.6% (n = 22) for the male sex. According to the age group, the old-old were the patients who performed the most PPR with 40.19% (n = 43). Most of the patients from Lima Norte underwent PPR treatment with 41.96% (n = 47). Conclusions: The removable prostheses predominated more than the fixed ones, being the PPR the one that was performed the most. It was also evidenced that the female sex received more prosthodontic treatments and that the place of origin that was most recorded was Lima Norte, possibly due to its proximity to the dental center.

The postabsorptive and postprandial metabolic rates of praying mantises: Comparisons across species, body masses, and meal sizes.

The metabolic rate of an animal affects the amount of energy available for its growth, activity and reproduction and, ultimately, shapes how energy and nutrients flow through ecosystems. Standard metabolic rate (SMR; when animals are post-absorptive and at rest) and specific dynamic action (SDA; the cost of digesting and processing food) are two major components of animal metabolism. SMR has been studied in hundreds of species of insects, but very little is known about the SMR of praying mantises. We measured the rates of CO2 production as a proxy for metabolic rate and tested the prediction that the SMR of mantises more closely resembles the low SMR of spiders - a characteristic generally believed to be related to their sit-and-wait foraging strategy. Although few studies have examined SDA in insects we also tested the prediction that mantises would exhibit comparatively large SDA responses characteristic of other types of predators (e.g., snakes) known to consume enormous, protein-rich meals. The SMR of the mantises was positively correlated with body mass and did not differ among the four species we examined. Their SMR was best described by the equation µW=1526*g0.745 and was not significantly different from that predicted by the standard 'insect-curve'; but it was significantly higher than that of spiders to which mantises are ecologically more similar than other insects. Mantises consumed meals as large as 138% of their body mass and within 6-12h of feeding and their metabolic rates doubled before gradually returning to prefeeding rates over the subsequent four days. We found that the SDA responses were isometrically correlated with meal size and the relative cost of digestion was 38% of the energy in each meal. We conclude that mantises provide a promising model to investigate nutritional physiology of insect predators as well as nutrient cycling within their ecological communities.

Remodeling of the chromatin structure of the facioscapulohumeral muscular dystrophy (FSHD) locus and upregulation of FSHD-related gene 1 (FRG1) expression during human myogenic differentiation.

BACKGROUND: Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant neuromuscular disorder associated with the partial deletion of integral numbers of 3.3 kb D4Z4 DNA repeats within the subtelomere of chromosome 4q. A number of candidate FSHD genes, adenine nucleotide translocator 1 gene (ANT1), FSHD-related gene 1 (FRG1), FRG2 and DUX4c, upstream of the D4Z4 array (FSHD locus), and double homeobox chromosome 4 (DUX4) within the repeat itself, are upregulated in some patients, thus suggesting an underlying perturbation of the chromatin structure. Furthermore, a mouse model overexpressing FRG1 has been generated, displaying skeletal muscle defects. RESULTS: In the context of myogenic differentiation, we compared the chromatin structure and tridimensional interaction of the D4Z4 array and FRG1 gene promoter, and FRG1 expression, in control and FSHD cells. The FRG1 gene was prematurely expressed during FSHD myoblast differentiation, thus suggesting that the number of D4Z4 repeats in the array may affect the correct timing of FRG1 expression. Using chromosome conformation capture (3C) technology, we revealed that the FRG1 promoter and D4Z4 array physically interacted. Furthermore, this chromatin structure underwent dynamic changes during myogenic differentiation that led to the loosening of the FRG1/4q-D4Z4 array loop in myotubes. The FRG1 promoter in both normal and FSHD myoblasts was characterized by H3K27 trimethylation and Polycomb repressor complex binding, but these repression signs were replaced by H3K4 trimethylation during differentiation. The D4Z4 sequences behaved similarly, with H3K27 trimethylation and Polycomb binding being lost upon myogenic differentiation. CONCLUSION: We propose a model in which the D4Z4 array may play a critical chromatin function as an orchestrator of in cis chromatin loops, thus suggesting that this repeat may play a role in coordinating gene expression.